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【结 构 式】 
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【分子编号】58526 【品名】3-hydroxy-2-phenyl-N-[(1S)-1-phenylpropyl]-4-quinolinecarboxamide 【CA登记号】 |
【 分 子 式 】C25H22N2O2 【 分 子 量 】382.46196 【元素组成】C 78.51% H 5.8% N 7.32% O 8.37% |
合成路线1
该中间体在本合成路线中的序号：(VI)The quinolinecarboxylic acid (III) was obtained by the Pfitzinger reaction of isatin (I) with 2-methoxyacetophenone (II) in ethanolic KOH at 80 C. Subsequent methyl ether cleavage in (III) using concentrated HI provided 3-hydroxy-2-phenylquinoline-4-carboxylic acid (IV). Coupling of acid (IV) with (S)-1-phenylpropylamine (V) by means of DCC and HOBt gave amide (VI). Ester (VIII) was then obtained by alkylation of the 3-hydroxy quinoline (VI) with ethyl bromoacetate (VII) in the presence of K2CO3 and KI. Finally, hydrolysis of the ethyl ester (VIII) with refluxing HCl afforded the corresponding carboxylic acid.
| 【1】 Giardina, G.A.M.; et al.; Discovery of a novel class of selective non-peptid. J Med Chem 1999, 42, 6, 1053. |
| 【2】 Giardina, G.A.M.; Grugni, M.; Raveglia, L.F.; Farino, C. (GlaxoSmithKline plc); Quinoline derivs.. EP 0876347; JP 2000501104; US 6277862; WO 9721680 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 14098 | 2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin | 91-56-5 | C8H5NO2 | 详情 | 详情 |
| (II) | 23641 | 2-methoxy-1-phenyl-1-ethanone | 4079-52-1 | C9H10O2 | 详情 | 详情 |
| (III) | 23642 | 3-methoxy-2-phenyl-4-quinolinecarboxylic acid | C17H13NO3 | 详情 | 详情 | |
| (IV) | 23643 | 3-hydroxy-2-phenyl-4-quinolinecarboxylic acid | 485-89-2 | C16H11NO3 | 详情 | 详情 |
| (V) | 23644 | (1S)-1-phenylpropylamine; (1S)-1-phenyl-1-propanamine | 3789-59-1 | C9H13N | 详情 | 详情 |
| (VI) | 58526 | 3-hydroxy-2-phenyl-N-[(1S)-1-phenylpropyl]-4-quinolinecarboxamide | C25H22N2O2 | 详情 | 详情 | |
| (VII) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (VIII) | 58527 | ethyl 2-{[2-phenyl-4-({[(1S)-1-phenylpropyl]amino}carbonyl)-3-quinolinyl]oxy}acetate | C29H28N2O4 | 详情 | 详情 |